Although the add-on therapy resulted in more adverse events than placebo, it was generally well tolerated, researchers report.

The new data are “exciting” because they represent another possible step toward US Food and Drug Administration (FDA) approval of this agent and give “new hope” to patients with LGS, lead researcher, Anup Patel, MD, associate professor of neurology and pediatrics, Nationwide Children’s Hospital and The Ohio State University Medical Center, Columbus, told Medscape Medical News.

“If approved, we will have another option to use in a disease state that tends to be very treatment-resistant,” he said.

The study results were released April 18 and will be presented in full at the American Academy of Neurology 2017 Annual Meeting (AAN) in Boston, Massachusetts.

LGS, a relatively rare type of epilepsy, typically develops between ages 3 and 5 years. It can be caused by many conditions, including a brain malformation, severe head injury, central nervous system infection, and an inherited degenerative or metabolic condition. In up to 30% of cases, no cause can be found. The condition is very drug resistant.

Patients with LGS often have multiple seizures types, including drop seizures. These are usually very brief atonic seizures in which the muscles suddenly become limp, causing head nods, loss of posture, and falling to the ground.

The multicenter study included 225 patients with LGS, with a mean age of 16 years (30% were adults; the oldest was 55 years old). These patients had experienced eight or more drop seizures during a 4-week baseline period, with failure of at least one AED.

Their median monthly drop seizure frequency was 85. A median of six AEDs had previously failed, and patients were currently taking a median of three AEDs.

Oral Formulation

The CBD agent, which does not contain tetrahydrocannabinol and so doesn’t have psychoactive properties, is a sesame oil–based, strawberry-flavored formulation delivered through a syringe. A 120-lb study participant would ingest about 2 teaspoons of the medicine twice daily.

The primary efficacy endpoint was percentage change from baseline in drop seizures, which tend to be the most prevalent type of seizures in patients with LGS, according to Dr Patel.

“More importantly, they are the most disabling type of seizures and have a greater risk of injury,” he said.

Of the total, 9 patients in the 20-mg/kg CBD group and 2 each in the 10-mg/kg CBD and placebo groups withdrew from the study early.

Adverse events occurred in 94% of the 20-mg/kg CBD group, 84% of the 10-mg/kg CBD group, and 72% of the placebo group. Most of these were mild or moderate. The two most common adverse events, occurring in greater than 10% of patients, were somnolence and decreased appetite.

Overall, 13 patients had elevated aminotransferase levels, which may indicate liver problems. But Dr Patel pointed out that 10 of these patients were also taking the AED valproic acid, which may have contributed to this elevation.

No patients died during the study.

Dr Patel pointed out that those in the placebo group as well as those taking the active agent had a high rate of adverse events.

“Obviously, the rate was higher in the treatment arms, but it was very similar to the overall percentage of [adverse events] noted in other trials of patients with LGS,” he said. “This is a very sick population of patients and they often have other problems.”

He also stressed that the number of patients who dropped out of the study was small.

Of the 212 completers, 99% entered the open-label extension study.

Study results of the drug in LGS have been released before, but what’s new here, said Dr Patel, is that researchers have added results on responder rates (a 50% or greater reduction in monthly drop seizures) and from the Caregiver Global Impression of Change (CGI) questionnaire, which is a sort of “marker for quality of life.”

The drug outperformed placebo on both these outcomes, said Dr Patel.

The responder rate was 15% in the placebo group vs 36% in the lower-dose CBD group (P = .0030) and 40% in the higher-dose group (P = .0006).

As for the CGI, 66% of patients taking the lower dose and 57% taking the higher dose reported an improvement in overall condition compared with 44% for placebo (P < .05 for both comparisons).

Also at the AAN meeting, researchers will be announcing results of a second blinded controlled trial comparing just the 20-mg/kg dose to placebo in patients with LGS. They will also be presenting results of similar research into the drug in patients with Dravet syndrome, another rare seizure disorder.

To date, GW Pharmaceuticals has received Orphan Drug Designation from the US Food and Drug Administration (FDA) for Epidiolex for the treatment of Dravet syndrome, LGS, tuberous sclerosis complex, and infantile spasms.

In addition, GW has received the FDA’s Fast Track Designation for the treatment of Dravet syndrome as well as Orphan Designation from the European Medicines Agency for Epidiolex in the treatment of Dravet syndrome and LGS.

Commenting on these findings for Medscape Medical News, Amy Brooks-Kayal, MD, chief and Ponzio Family Chair in Pediatric Neurology, University of Colorado, Denver, and former president of the American Epilepsy Society (AES), pointed out that these results are similar to the seizure reductions reported in several abstracts presented in December 2016 at the AES meeting in Houston, Texas.

“These results suggest that CBD may be an effective adjunctive therapy in treatment-resistant epilepsy, and can be effective in reducing seizure frequency, but with a high rate of adverse effects and low rate of seizure freedom,” she said.